Polymorphism refers to a different solid form (such as a diamond and a graphite) formed from the same elements or molecules spatially arranged in different ways. The difference in arrangement can come from different accumulation ways of space elements or molecules, or different conformational isomers due to the structural flexibility of the molecules themselves, which thereby leads to differences in spatial arrangement. However, such differences in arrangement will lead to different crystal forms with different solubility, physical and chemical stability, reactivity, mechanical stability and morphology.
The changes of the solid state in crystalline drugs or foods may be occurred during processing or storage. This is mainly due to the fact that various process treatments of APIs are usually involved in the preparation process, and the external stimulus is typically from mechanical crushing, grinding, compression moulding or tableting process, freezing, drying, melting and the like. In addition, drugs or food may absorb moisture during storage, interact with oxygen in the air, decompose impurities and interact with excipients and so on.
The changes in the crystalline form can lead to changes in various solid-state chemistry related properties, such as lattice volume, density, viscosity, surface tension, hardness, crystal morphology, color, refractive index, melting point, heat of solution, solubility, dissolution rate, stability, hygroscopicity and chemical reaction performance and so on. Importantly, different crystal forms may lead to changes in drug dissolution, dissolution performance, pharmacokinetics, and bioavailability, thereby affecting the efficacy and safety of drug. Meanwhile, on the food side, different crystal forms may lead to changes in color, morphology, stability and hygroscopicity, which thereby affect the storage conditions, taste and sensory evaluation of food. Therefore, it is of great importance in the process of food and drug research and development to compare the hygroscopicity, chemical stability and workability of different crystal forms, and then select the optimal crystal form.
The structure of Rebaudioside D (RD) is as shown below:

Rebaudioside D (RD), a steviol glycoside compound extracted from stevia, is about 200 times as sweet as sucrose and is considered as a potential sweetener. Among the steviol glycoside compound, Rebaudioside A has been widely used as a sweetener in beverage applications but has a problem of bad taste, whereas Rebaudioside D has a better sugar characteristic and more desirable flavor than Rebaudioside A.
A study in the journal of “Journal of Agricultural and Food Chemistry” entitled “Human Psychometric and Taste Receptor Responses to Steviol Glycosides” shows that the sweetness of Rebaudioside D is strongest, and the bitter is weaker compared to Rebaudioside A, Rebaudioside B, Rebaudioside C, Rebaudioside E and Rebaudioside F.
In addition, it is reported in patent of CN 102894325 A that Rebaudioside D can be used to improve the existing sweeteners, especially the taste and flavor of a steviol glycoside in the natural sweeteners. The improved sweetener has a similar taste with sucrose, no bitter and astringency, no artificial synthetic ingredients and energy components are added, and the natural and energy-free characteristics of a steviol glycoside and Rebaudioside A are maintained. However, the low water solubility of Rebaudioside D at room temperature (300 to 450 ppm) limits its use in the food, beverage, flavoring, brewing, pharmaceutical and other industries. Although the preparation and extraction method for Rebaudioside D are reported in CN 104159908 A and CN 103709215 A, respectively, the crystal form of Rebaudioside D has never been reported. Different crystal forms may lead to differences in color, morphology, stability, hygroscopicity and solubility, which thereby affect the storage conditions, taste and sensory evaluation of the food. Different preparation method will make the obtained crystal forms unpredictable. Therefore, it is of great importance to optimize and control the conditions to obtain the optimal crystal form in the development of food and medicine.
There is an urgent need in the art to provide a crystal form of Rebaudioside D with a better property, such as a new crystal form with a good crystallinity, a good water solubility, a high chemical stability. Meanwhile, there is an urgent need to provide a preparation method and a use of the above-mentioned crystal forms.